The exact eurobiological factors [that drive problem drinking and contribute to relapse to hazardous drinking] remain unidentified. Understanding the neurochemistry that underlies [alcoholism and relapse] will ultimately result in more effective treatment strategies. Recent research has indicated that the neurotransmitter dopamine (DA) is involved in attributing salience to rewards: reward salience may determine how much an individual pays attention to a reward and how much an individual "wants" a reward. Several theories of addiction suggest that abnormally high "salience" attribution to alcohol [is a key factor in development of hazardous drinking, and may place an important role in explaining why some recovering alcoholics relapse.] [The DA salience signal response to rewards may prove to be a useful tool for development of therapeutic interventions and prediction of treatment response.] We propose that alterations in salience attribution are related to the development of alcoholism, and that DA responses to alcohol reward are indicative of salience attribution. The long-term goal of this work is increase our understanding of how DA is involved in the [unconscious processes that lead to chronic and excessive alcohol consumption]. The primary objective of this proposal is to compare the striatal DA responses to [predicted and unpredicted IV alcohol administration between nontreatment-seeking alcoholics (NTS) and social drinkers (SD). The central hypothesis of this proposal is that NTS subjects have abnormal salience attribution to alcohol that is mediated by striatal DA.] We will test the following specific hypotheses: [(1) NTS subjects will have increases in DA in response to expected IV alcohol but SD will not;(2) Unexpected (highly salient) IV alcohol administration will result in a greater magnitude of DA release in NTS compared to SD;(3) Unexpected caffeine administration will result in increases in DA in SD, but not NTS. Additionally, the dataset we collect will permit testing of a fourth, secondary hypothesis, which is to determine whether alcohol and smoking have an additive effect on deficits in striatal D2 receptor availability.] Changes in striatal DA levels will be detected using PET scanning and [11C]raclopride, a DA D2/D3 receptor ligand that is sensitive to changes in endogenous dopamine levels. Sixty social drinkers and sixty nontreatment- seeking alcoholics will each receive two PET scans. One scan will be acquired during a baseline state, the other during [either (i) an expected IV alcohol infusion to a target breath alcohol concentration of 80 mg%, (ii) an unexpected IV alcohol infusion, or (iii) an unexpected IV caffeine infusion.] Quantitation of changes in DA levels will be achieved by calculating the change in D2/D3 receptor availability from the [challenge] scan relative to the baseline scan. The knowledge to be gained from the extension of this work will significantly advance the field of alcohol research by providing novel and important information about how striatal DA signaling is related to hazardous alcohol consumption. PUBLIC HEALTH RELEVANCE: The neurotransmitter dopamine [is involved in communicating the importance of rewarding stimuli.] Characterizing the role of dopamine responses to alcohol reward in social drinkers and nontreatment-seeking alcoholics will provide new and important information about the neurochemical processes involved in alcoholism. The knowledge to be gained from this proposal will set the stage for future studies which will use dopamine responses to reward to investigate [(1) if effective treatments for alcoholism modulate the DA salience response, (2) if the DA salience response can be used to identify alcoholic individuals who are likely to respond to treatment and individuals who are likely to relapse, and (3) if the DA salience response can be used to provide personalized treatment plans for alcoholism in order to maximize clinical response.